CircDIP2C ameliorates oxidized low-density lipoprotein-induced cell dysfunction by binding to miR-556-5p to induce TET2 in human umbilical vein endothelial cells.

Circular RNAs (circRNAs) are a group of conserved noncoding RNAs. Recent reports reveal that circRNAs play vital parts in cardiovascular system, including atherosclerosis (AS). The present study is designed to reveal the role of circRNA DIP2C-disco interacting protein 2 homolog C (circDIP2C) in oxidized low-density lipoprotein (ox-LDL)-triggered damage of human umbilical vein endothelial cells (HUVECs). The expression levels of circDIP2C, microRNA-556-5p (miR-556-5p) and tet methylcytosine dioxygenase 2 (TET2) were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Protein expression was determined by western blot analysis. Cell viability and angiogenesis were demonstrated by cell counting kit-8 and tube formation assays, respectively. The levels of reactive oxygen species (ROS) and malondialdehyde (MDA) were checked by ROS and MDA determination assays. Superoxide dismutase (SOD) and lactate dehydrogenase (LDH) activity assays were performed to detect the activity of SOD and LDH. The binding sites of miR-556-5p in circDIP2C or TET2 were predicted by online databases, and identified by dual-luciferase reporter, RNA immunoprecipitation and RNA pull-down assays. CircDIP2C and TET2 expression were obviously decreased, while miR-556-5p expression was increased in ox-LDL-induced HUVECs in comparison with untreated HUVECs. Ox-LDL treatment inhibited cell viability and angiogenesis, promoted oxidative stress, enhanced cytotoxicity and activated NLR family pyrin domain containing 3 (NLRP3) inflammasome pathway. CircDIP2C upregulation protected HUVECs from ox-LDL-induced injury. Additionally, circDIP2C directly bound to miR-556-5p, which was further found to target TET2. MiR-556-5p mimics or TET2 silencing could attenuate the effect of circDIP2C overexpression on ox-LDL-induced cell disorder. Thus, we came a conclusion that circDIP2C protected against ox-LDL-induced HUVEC damage by upregulating TET2 expression through sponging miR-556-5p, which provided a strategy for the therapy of AS.